Bone adaptation: Safety factors and load predictability in shaping skeletal form

Much is known about skeletal adaptation in relation to the mechanical functions that bones serve. This includes how bone adapts to mechanical loading during an individual's lifetime as well as over evolutionary time. Although controlled loading in animal models allows us to observe short-term bone adaptation (epigenetic mechanobiology), examining an assemblage of extant vertebrate bones or a group of fossils' bony structures can reveal the combined effects of long-term trends in loading history and the effects of natural selection. In this survey we examine adaptations that take place over both time scales and highlight a few of the extraordinary insights first published by John Currey. First, we provide a historical perspective on bone adaptation control mechanisms, followed by a discussion of safety factors in bone. We then summarize examples of structural- and material-level adaptations and mechanotransduction, and analyze the relationship between these structural- and material-level adaptations observed in situations where loading modes are either predictable or unpredictable. We argue that load predictability is a major consideration for bone adaptation broadly across an evolutionary timescale, but that its importance can also be seen during ontogenetic growth trajectories, which are subject to natural selection as well. Furthermore, we suggest that bones with highly predictable load patterns demonstrate more precise design with lower safety factors, while bones that experience less predictable loads or those that are less capable of repair and adaptation are designed with a higher safety factor. Finally, exposure to rare loading events with high potential costs of failure leads to design of structures with very high safety factor compared to everyday loading experience. Understanding bone adaptations at the structural and material levels, which take place over an individual's lifetime or over evolutionary time has numerous applications in translational and clinical research to understand and treat musculoskeletal diseases, as well as to permit the furthering of human extraterrestrial exploration in environments with altered gravity.